Chemically strengthened bioactive glass-ceramics

ABSTRACT

A chemically strengthened bioactive glass-ceramic composition as defined herein. Also disclosed are methods of making and using the disclosed compositions.

This application claims the benefit of priority under 35 U.S.C. § 119 ofU.S. Provisional Patent Application No. 62/591,438 filed Nov. 28, 2017,the content of which is incorporated herein by reference in itsentirety.

CROSS REFERENCE TO RELATED APPLICATIONS

The disclosure relates to commonly owned and assigned US ProvisionalPatent Application Nos.:

-   -   62/342,384, filed May 27, 2016, entitled “BIOACTIVE        ALUMINOBORATE GLASSES”;    -   62/342,377, filed May 27, 2016, entitled “MAGNETIZABLE GLASS        CERAMIC COMPOSITION AND METHODS THEREOF”;    -   62/342,381, filed May 27, 2016, entitled “LITHIUM DISILICATE        GLASS-CERAMIC COMPOSITIONS AND METHODS THEREOF”;    -   62/342,391, filed May 27, 2016), entitled “BIODEGRADABLE        MICROBEADS”;    -   62/342,411, filed May 27, 2016, entitled “BIOACTIVE GLASS        MICROSPHERES”; and    -   62/342,426, filed May 27, 2016, entitled “BIOACTIVE        BOROPHOSPHATE GLASSES”; but does not claim priority thereto.

The disclosure also relates, but does not claim priority to, commonlyowned and assigned patent applications

-   -   61/941,677, entitled “ANTIMICROBIAL GLASS COMPOSITIONS, GLASSES        AND ARTICLES INCORPORATING THE SAME”, and    -   61/941,690, entitled “ANTIMICROBIAL GLASS COMPOSITIONS, GLASSES        AND POLYMERIC ARTICLES INCORPORATING THE SAME,” both filed Feb.        19, 2014, both mention Cu containing compositions having        articles having antimicrobial properties; and    -   Corning patent application Ser. No. 14/623,674, now US Pat Pub.        20150239772, entitled “LOW CRYSTALLINITY GLASS-CERAMICS”, which        mentions crystallisable glasses and glass-ceramics that exhibit        a black color and are opaque.

The present application is also related commonly owned and assigned USSNApplication Nos.:

62/591,423 filed Nov. 28, 2017, entitled “BIOACTIVE GLASS COMPOSITIONSAND METHODS OF TREATING DENTIN HYPERSENSITIVITY”;

-   -   62/591,446 filed Nov. 28, 2017, entitled “HIGH LIQUIDUS        VISCOSITY BIOACTIVE GLASS”; and    -   62/591,429, filed Nov. 28, 2017, entitled “BIOACTIVE BORATE        GLASS AND METHODS THEREOF”, filed concurrently herewith, but        does not claim priority thereto.

The entire disclosure of each publication or patent document mentionedherein is incorporated by reference.

BACKGROUND

The disclosure relates to chemically strengthened bioactiveglass-ceramics, and method of making and using the glass-ceramics.

SUMMARY

In embodiments, the disclosure provides a method of making aglass-ceramic article, including a chemical strengthening process thatimproves the flexural strength of lithium disilicate glass-ceramics. Theglass-ceramic articles can be ion exchanged in, for example, NaNO₃ orKNO₃ for a suitable time. Both Li₂O and Na₂O ions in the residual glasscan be ion exchanged.

In embodiments, the disclosure provides a chemically strengthenedbioactive glass-ceramic based on lithium disilicate, apatite, andwollastonite.

In embodiments, the disclosure provides a glass-ceramic article having aflexural strength of over 1000 MPa, which strength can be achieved afterion exchange. The strength is comparable to ZrO₂ ceramics.

In embodiments, the disclosure provides an ion-exchanged glass-ceramicshaving bioactivity that is retained even after the ion-exchangestrengthening process.

In embodiments, the disclosure provides glass-ceramic compositionshaving lithium disilicate as the primary major crystal phase, and atleast one of wollastonite, fluorapatite, cristobalite, β-quartz,lithiophosphate, or mixtures thereof as minor phases. The compositionscan comprise, for example, 50 to 75% SiO₂, 1 to 5% Al₂O₃, 0.1 to 10%B₂O₃, 5 to 20% Li₂O, 0.5 to 5% Na₂O, 0 to 4% K₂O, 0.5 to 8% ZrO₂, and0.1 to 1.0% F⁻ (i.e., fluoride ion) (i.e., fluoride ion), based on a 100wt % total of the composition.

BRIEF DESCRIPTION OF THE DRAWINGS

In embodiments of the disclosure:

FIG. 1 shows a comparison of flexural strength of a lithium disilicateglass-ceramic (i.e., Example composition 9) before (dots) and after(squares) ion exchange.

FIG. 2 shows a comparison of flexural strength of selected comparativematerials (e.g., 200 to 260 as defined herein) used for biomedicalapplications including an ion-exchanged glass-ceramic of the presentlydisclosed composition (270).

FIGS. 3A to 3I show a cell culture study on glass-ceramics before (3A to3C) and after ion-exchanging (“IOX”) (3D to 3F).

DETAILED DESCRIPTION

Various embodiments of the disclosure will be described in detail withreference to drawings, if any. Reference to various embodiments does notlimit the scope of the invention, which is limited only by the scope ofthe claims attached hereto. Additionally, any examples set forth in thisspecification are not limiting and merely set forth some of the manypossible embodiments of the claimed invention.

In embodiments, the disclosed method of making and using provide one ormore advantageous features or aspects, including for example asdiscussed below. Features or aspects recited in any of the claims aregenerally applicable to all facets of the invention. Any recited singleor multiple feature or aspect in any one claim can be combined orpermuted with any other recited feature or aspect in any other claim orclaims.

Definitions

“IOX,” “IX,” “IOXing,” “IOX'ed,” “IOX'd,” “ion-exchange,”“ion-exchanged,” “ion-exchanging,” or like terms refer to the ionexchange of ions, partially or completely, on at least a portion of theglass or glass-ceramic surface, on one or both sides as specified, withdifferent ions such as an ion having a larger atomic radius compared tothe exchanged ions such as K⁺ ions exchanged (i.e., replacing) for Na⁺ions (see also, for example, U.S. Pat. Nos. 3,790,430, and 3,778,335).

“Glass,” “glass-ceramic,” or like terms can refer to the disclosed glassprecursor or the disclosed glass-ceramic product compositions that hasbeen either strengthened or un-strengthened.

“Glass article,” “glass-ceramic article,” or like terms can refer to anyobject made wholly or partly of any of the disclosed glass orglass-ceramic compositions.

“Bioactivity Index” “index of bioactivity,” “I_(B),” or like terms orsymbols refer to, for example, the time for more than 50% of theinterface of a specific bioactive material to be bonded by a biologicalmaterial such as bone, tissue, and like materials. Mathematically, abioactivity index (according to Hench; see Cao, W., et al., BioactiveMaterials, Ceramics International, 22 (1996) 493-507) is,I_(B)=100/t_(0.5bb), where t_(0.5bb) is the time for more than 50% of abioactive material's interface, such as an implant, to be bonded by abiological material such as bone, tissue, and like materials, includingosteoproductive (Class A having both intracellular and extracellularresponses, e.g., 45S5 Bioglass®) and osteoconductive (Class Bextracellular response only at interface, e.g., synthetichydroxyapatite) materials.

“Include,” “includes,” or like terms means encompassing but not limitedto, that is, inclusive and not exclusive.

“About” modifying, for example, the quantity of an ingredient in acomposition, concentrations, volumes, process temperature, process time,yields, flow rates, pressures, viscosities, and like values, and rangesthereof, or a dimension of a component, and like values, and rangesthereof, employed in describing the embodiments of the disclosure,refers to variation in the numerical quantity that can occur, forexample: through typical measuring and handling procedures used forpreparing materials, compositions, composites, concentrates, componentparts, articles of manufacture, or use formulations; through inadvertenterror in these procedures; through differences in the manufacture,source, or purity of starting materials or ingredients used to carry outthe methods; and like considerations. The term “about” also encompassesamounts that differ due to aging of a composition or formulation with aparticular initial concentration or mixture, and amounts that differ dueto mixing or processing a composition or formulation with a particularinitial concentration or mixture.

“Optional” or “optionally” means that the subsequently described eventor circumstance can or cannot occur, and that the description includesinstances where the event or circumstance occurs and instances where itdoes not.

The indefinite article “a” or “an” and its corresponding definitearticle “the” as used herein means at least one, or one or more, unlessspecified otherwise.

Abbreviations, which are well known to one of ordinary skill in the art,may be used (e.g., “h” or “hrs” for hour or hours, “g” or “gm” forgram(s), “mL” for milliliters, and “rt” for room temperature, “nm” fornanometers, and like abbreviations).

Specific and preferred values disclosed for components, ingredients,additives, dimensions, conditions, times, and like aspects, and rangesthereof, are for illustration only; they do not exclude other definedvalues or other values within defined ranges. The composition andmethods of the disclosure can include any value or any combination ofthe values, specific values, more specific values, and preferred valuesdescribed herein, including explicit or implicit intermediate values andranges.

Bioactive materials with high strength and toughness are in significantdemand for the regeneration of bone and teeth. Glass-ceramics based onlithium disilicate offer desirable mechanical properties, including highbody strength and fracture toughness, due to their microstructures ofrandomly-oriented interlocking crystals. Flexural strength in the rangeof 300 to 400 MPa is reported for lithium disilicate glass-ceramics (W.Holand, et al., A Comparison of the Microstructure and Properties of theIPS EmpressT2 and the IPS EmpressT Glass-Ceramics, J Biomed Mater Res(Appl Biomater), 2000, 53: 297-303; W. Liena, et al., Microstructuralevolution and physical behavior of a lithium disilicate glass-ceramic,Dent Mater 2015, 31: 928-940), which makes them suitable forapplications in the fabrication of single and multiple dentalrestorations. Furthermore, the superior aesthetics and the ability toform a monolithic structure make lithium disilicate a viable option fordental patients. However, the low flexural strength of lithiumdisilicate makes them less suitable for applications where stressconcentration can be high (see Zhang Y., et al., Chipping resistance ofgraded zirconia ceramics for dental crowns. J Dent Res, 2012,91:311-315). In comparison, ZrO₂ ceramics are reported to have aflexural strength over 1000 MPa (see Zhang supra., and F. Succaria, etal., Prescribing a dental ceramic material: Zirconia vslithium-disilicate. Saudi Dent J, 2011, 23: 165-166). They can be usedas multi-unit bridges for dental restoration. However, the lack of hightranslucency and the lower ability to match the appearance of naturalteeth remain challenges for ZrO₂ ceramics in dental restorations (seeSuccaria, supra.). There is a significant need of glass-ceramics havingimproved strength while maintaining their: aesthetic attributes, ease informing, and machine ability.

Glass strengthening by ion exchange (chemical tempering) has been widelyused to improve the mechanical strength and product reliabilities in avariety of glass and glass-ceramics (see R. Gy, “Ion exchange for glassstrengthening,” Mater Sci Eng B, 2008, 149: 159-165; and R. J. Araujo,“Strengthening glass by ion exchange,” U.S. Pat. No. 5,674,790A, 1997).In this process, glass articles are immersed into a molten alkali saltat a temperature below the glass transition to allow the alkali ionsfrom the glass surface to exchange for those from the molten salt. Thelarger ionic radius of penetrating ions than the ions leaving the glassresults in the strengthening of the glasses. As a result, theintroduction of surface compression strengthens glasses and effectivelyreduces the probability of breakage from surface flaws (see V. M.Sglavo, “Chemical strengthening of soda lime silicate float glass:effect of small differences in the KNO₃ bath,” Int J Appl Glass Sci,2015, 6: 72-82). This strengthening technique has been widely used inglass products including aircraft cockpit windshields, transparentarmor, glass container, and information technology devices (cell phonesand tablets) (see M. Jacoby, “New Applications for Glass Emerge,” Chem.Eng. News, 90 [25] 34-36 (2012)). However, the lithium disilicate phaseis not ion exchangeable due to the lack of mobile ions in itsmicrostructure.

In embodiments, the disclosure provides a method for improving theflexural strength of lithium disilicate glass-ceramics throughchemically strengthening (ion exchange) of the residual glass phase inthe material. The flexural strength of glass-ceramics is more thandoubled after ion exchange, which makes the flexural strength of theproduct glass-ceramic comparable to ZrO₂ ceramics. The glass-ceramicshave excellent bioactivity.

In embodiments, the disclosure provides a glass-ceramic composition,comprising: a first crystalline phase and a second crystalline phase, incombination, comprise a source of:

-   -   50 to 75 wt % SiO₂,    -   1 to 5 wt % Al₂O₃,    -   0.1 to 10% B₂O₃,    -   5 to 20 wt % Li₂O,    -   0.5 to 5 wt % Na₂O,    -   0.1 to 4% K₂O,    -   0.5 to 6 wt % P₂O₅    -   0.5 to 8% ZrO₂, and    -   0.1 to 1.0 wt % F⁻, based on a 100 wt % total of the        composition.

In embodiments, the disclosure provides a glass-ceramic compositionwhere the source is:

-   -   50 to 70 wt % SiO₂,    -   1 to 4 wt % Al₂O₃,    -   0.1 to 4% B₂O₃,    -   6 to 18 wt % Li₂O,    -   1 to 4 wt % Na₂O,    -   0.1 to 3% K₂O,    -   1 to 5 wt % P₂O₅    -   1 to 6% ZrO₂, and    -   0.1 to 1.0 wt % F⁻, based on a 100 wt % total of the        composition.

In embodiments, the glass-ceramic composition can further comprisehaving composition particles that have ion-exchanged surfaces having areduced lithium ion (Li⁺) concentration and having at least one of anelevated sodium (Na⁺) concentration, an elevated potassium (K⁺)concentration, or an elevated concentrations of lithium ion (Li⁺) andsodium ion (Na⁺).

In embodiments, the glass-ceramic composition can have a firstcrystalline phase that comprises of from 50 to 99 wt % and a secondcrystalline phase that comprises of from 1 to 50 wt % based on a 100 wt% total of the composition.

In embodiments, the disclosure provides a glass-ceramic composition,comprising: a first crystalline phase and a second crystalline phase, incombination, comprising:

-   -   55 to 65 wt % SiO₂,    -   2 to 4 wt % Al₂O₃,    -   8 to 16 wt % Li₂O,    -   1 to 4 wt % Na₂O,    -   0.1 to 2% K₂O,    -   2 to 5 wt % P₂O₅    -   1 to 5% ZrO₂, and    -   0.1 to 1.0 wt % F−, based on a 100 wt % total of the        composition.

In embodiments, the disclosure provides a glass-ceramic compositionwhere the composition is free of B₂O₃.

In embodiments, the disclosure provides a glass-ceramic comprising:

-   -   50 to 75 wt % SiO₂,    -   1 to 5 wt % Al₂O₃,    -   0.1 to 10% B₂O₃,    -   5 to 20 wt % Li₂O,    -   0.5 to 5 wt % Na₂O,    -   0.1 to 4% K₂O,    -   0.5 to 6 wt % P₂O₅    -   0.5 to 8% ZrO₂, and    -   0.1 to 1.0 wt % F⁻, based on a 100 wt % total of the        composition.

In embodiments, the source or precursor batch composition has the samecomposition as the glass-ceramic. The bulk composition is essentiallystill the same composition after ion exchange. Only the surfacecomposition changes as a result of surface ion exchange.

In embodiments, the glass-ceramic composition as an article has aflexural strength of from 300 to 2,000 MPa.

In embodiments, the disclosure provides a method of making aglass-ceramic article comprising:

forming a melt mixture of a source of:

-   -   50 to 75 wt % SiO₂,    -   1 to 5 wt % Al₂O₃,    -   0.1 to 10% B₂O₃,    -   5 to 20 wt % Li₂O,    -   0.5 to 5 wt % Na₂O,    -   0.1 to 4% K₂O,    -   0.5 to 6 wt % P₂O₅    -   0.5 to 8% ZrO₂, and    -   0.1 to 1.0 wt % F⁻, based on a 100 wt % total of the composition        to form a glass-ceramic article; and    -   at least one chemical strengthening of the resulting        glass-ceramic article.

In embodiments, the at least one chemical strengthening of the resultingglass-ceramic article can be accomplished by ion exchanging in NaNO₃, inKNO₃, or in a mixture thereof, for a suitable time, to reduce theconcentration of lithium ion, sodium ion, or both, on the surface of theglass-ceramic article.

In embodiments, the article can be, for example, a suitable geometry orform factor, for example, a pattie, a dimensioned portion cut from apattie, for example, a disc, a monolith, a plurality of particles, adrawn sheet, and like form factors, or combinations thereof.

In embodiments, the article has bioactivity before ion-exchanging.

In embodiments, the article has bioactivity after ion-exchanging.

The present disclosure is advantaged in several aspects, including forexample:

-   -   lithium disilicate glass-ceramics having strengths comparable to        ZrO₂ ceramics can be achieved after ion exchange; and    -   the ion exchange process does not compromise the bioactivity of        the disclosed glass-ceramics.

In embodiments, the disclosure provides a method of making lithiumdisilicate glass-ceramics that includes a chemically strengthening(e.g., ion exchange), and results in a glass-ceramic having increasedflexural strength. The flexural strength of the disclosed glass-ceramiccompositions is more than doubled after ion-exchange, e.g., to over 1000MPa, which is comparable to that of ZrO₂ ceramics. The high flexuralstrength enables the use of the disclosed lithium disilicateglass-ceramic compositions in multi-unit bridges for dental restoration.Unexpectedly, the disclosed chemical strengthening step does not impactthe bioactivity of the resulting strengthened lithium disilicateglass-ceramic. The major phase in the disclosed glass-ceramics islithium disilicate, and minor phases can be, for example, fluoroapatiteand wollastonite. Both fluoroapatite and wollastonite are beneficial tothe attachment and growth of osteoblastic cells.

In embodiments, the precursor glasses can comprise, for example, 50to75% SiO₂, 1 to 5% Al₂O₃, 0.1 to 10% B₂O₃, 5 to 20% Li₂O, 0.5 to 5%Na₂O, 0 to 4% K₂O, 0.5 to 8% ZrO₂, and 0.1 to 1.0% F⁻ based on the totalweight percentage of 100 wt % (see Table 1).

In embodiments, the flexural strength of the lithium disilicateglass-ceramics can be improved by, for example, a factor of two as aresult of the ion exchange treatment. By ion exchanging in KNO₃ at 470°C. for 4 hr, the flexural strength of an example glass-ceramicComposition 9 was increased from 485 MPa to 1150 MPa (squares). Inembodiments, the mechanical reliability (i.e., the probability ofsuccess: Reliability=1−Probability of Failure) was also improved asmeasured by an increase of the Weibull modulus (a dimensionlessparameter of the Weibull distribution, which is used to describevariability in measured material strength of brittle materials), from 4to over 120 (see FIG. 1). The flexural strength of the ion-exchangedglass-ceramic of the disclosure (e.g., 270) was much higher than acommercially available bioactive glass (i.e., 45S5 Bioglass®) (200),glass-ceramics (Biovert (210), A/W (230) (see L. L. Hench,“Bioceramics,” J Am Ceram Soc, 1998, 81: 1705-1728), IPS e.max (240),and IPS e.max CAD (250) (Fu, et al., “Nature-inspired design of strong,tough glass-ceramics,” MRS Bulletin, 2017, 42:220-225), or ceramics HA(220). The flexural strength of the ion-exchanged glass-ceramic of thedisclosure (e.g., 1150) was comparable to ZrO₂ ceramics (1000) (FIG. 2)(Fu, et al., MRS Bulletin, supra.). The flexural strength of thedisclosed glass-ceramic compositions make them suitable biomaterialcandidates for use in, for example, dental multi-unit bridges.

FIGS. 3A to 3I show a cell culture study on glass-ceramics before (3A to3C) and after ion-exchanging (“IOX”) (3D to 3F). Cell morphology isevident for the un-ion-exchanged Example Composition 9 after: a) one day(3A), b) four days (3B), and c) seven days (3C). A similar cellmorphology was observed on IOX'd parts (KNO₃, 470° C. for 4 hr) after:d) one day (3D); e) four days (3E); and f) seven days (3F). Comparablecell morphology was seen on TCT culture plates after: g) one day (3G);h) four days (3G); and i) seven days (3I). A MC3T3 cell line was usedfor cell culture test.

In embodiments, the bioactivity of the disclosed lithium disilicatecontaining articles was substantially or entirely retained after anion-exchange strengthening step. Cell attachment and cell growth wereclearly observed on the surfaces of the disclosed glass-ceramic articleswith and without ion-exchange (FIG. 3). No visible difference in cellattachment at day 1, and cell expansion at day 4 and day 7 was observedbetween the non-ion-exchanged and the ion-exchanged materials. The cellmorphology was also similar to those cultured on a Tissue CultureTreated® (TCT) culture wells. “TCT” refers to a tissue culture treatedmicroplate substrate available from Corning, Inc®.

In embodiments, both Li₂O and Na₂O in residual glass phase can be ionexchanged to create a compressive stress layer in the surface of theware to further improve mechanical strength.

Tables 1 and 2 list examples of the as-batched compositions. Theceramming cycle for each of the samples 1 to 15 was 700° C. at 2 hr and800° C. at 4 hr.

TABLE 1 Examples of As-batched compositions.² Oxides (wt %) 1 2 3 4 5 67 8 SiO₂ 70 65 60 55 60 60 70 65 B₂O₃ 0 0 0 0 0 0 0 0 Al₂O₃ 2.5 2.5 2.52.5 2.5 2.5 2.5 2.5 Li₂O 12 12 12 12 15 12 12 12 Na₂O 2 2 2 2 2 2 2 2CaO 6 6 6 6 6 6 6 6 P₂O₅ 4 4 4 4 4 4 4 4 ZrO₂ 2 2 2 2 2 4 2 2 F⁻ 0 0 0 00 0 0.5 0.5 Phase assemblage¹ A A A B C D E E Flexural strength — — — —— — 504 407 (MPa) Fracture toughness — — — — — — 1.8 1.9 (MPa ·m{circumflex over ( )}0.5)

TABLE 2 Examples of As-batched compositions.² Oxides (wt %) 9 10 11 1213 14 15 SiO₂ 60 55 60 60 60 60 60 B₂O₃ 0 0 0 0 2 4 6 Al₂O₃ 2.5 2.5 2.52.5 2.5 2.5 2.5 Li₂O 12 12 15 12 12 12 12 Na₂O 2 2 2 2 2 2 2 CaO 6 6 6 66 6 6 P₂O₅ 4 4 4 4 4 4 4 ZrO₂ 2 2 2 4 2 2 2 F⁻ 0.5 0.5 0.5 0.5 0.5 0.50.5 Phase assemblage¹ I G J H I I I Flexural strength 485 303 — — — — —(MPa) Fracture toughness 2.2 2.2 — — — — — (MPa · m{circumflex over( )}0.5) ¹Phase assemblage key for compositions of Tables 1 and 2: A =Lithium disilicate, cristobalite, wollastonite, β-quartz,lithiophosphate. B = Lithium disilicate, wollastonite, lithiophosphate.D = Lithium disilicate, β-quartz, lithiophosphate. E = Lithiumdisilicate, cristobalite, fluorapatite, β-quartz. G = Lithiumdisilicate, fluorapatite, lithium metasilicate, β-quartz. H = Lithiumdisilicate, fluorapatite, β-quartz. I = Lithium disilicate,fluorapatite, β-quartz, lithiophosphate. J = Lithium disilicate, lithiummetasilicate, fluorapatite, β-quartz. ²Sample Appearance: Samples ofExamples 1 to 8 and 10 to 15 were translucent white; Example 9 wastranslucent/semi-transparent white.

Raw materials, equipment, or both, used to produce the compositions ofthe present disclosure, can introduce certain impurities or componentsthat are not intentionally added, and can be present in the final glasscomposition. Such materials can be present in the disclosed compositionsin minor amounts and are referred to as “tramp materials.”

Disclosed compositions can comprise the tramp materials, typically intrace amounts. Similarly, “iron-free,” “sodium-free,” “lithium-free,”“zirconium-free,” “alkali earth metal-free,” “heavy metal-free,” or likedescriptions, mean that the tramp material was not purposefully added tothe composition, but the composition may still comprise iron, sodium,lithium, zirconium, alkali earth metals, or heavy metals, etc., but inapproximately tramp or trace amounts.

Unless otherwise specified, the concentrations of all constituentsrecited herein are expressed in terms of weight percent (wt %).

EXAMPLES

The following Examples demonstrate making, use, and analysis of thedisclosed compositions and methods in accordance with the above generalprocedures.

Example 1

Preparation of Actual Example Glass-Ceramic Compositions

Example Glass-Ceramic Compositions 1 to 15 listed in Tables 1 and 2, andtheir respective source batch materials in the indicated amounts,including for example, silica, boric acid, alumina, lithium carbonate,sodium carbonate, limestone, spodumene, aluminum metaphosphate, wereindividually combined and melted in an electric furnace. Prior tomelting, the batch source materials were vigorously mixed in a plasticjar using a Turbula® mixer. Then the mixtures were transferred to aplatinum crucible with an internal volume of approximately 650 cc andheated at 1350° C. for 6 hr, and then the glass melt was poured on asteel plate, and annealed at 500° C. to produce an article in the formof a pattie. Alternatively, the glass melt can be drawn into aglass-ceramic sheet article or a fiber article. The resulting articlewas ion-exchanged before or after further processing and as mentioned inExample 2.

Example 2

Further Processing of the Pattie Article of the Bioactive Composition ofExample 1

The pattie or sheet of Example 1 was further processed into other usefulforms, for example: cutting to produce a portion cut from a pattie suchas a disc, or a monolith to desired dimensions; crushing to produce aplurality of particles by, for example, any suitable crushing orpulverizing equipment. The resulting article was ion-exchanged before orafter the further processing mentioned here.

Example 3

Method of Attachment and Growth of Bone Cells with the BioactiveComposition of Example 1

Ion exchanged glass ceramic discs (12.5 mm in diameter×1 mm thick),obtained from disc cutting and ion-exchange mentioned in Example 2 anddescribed further below, were placed into wells of 24 well microplates.MC3T3 cells were seeded to each well at a density of 10 K/well andcultured for 1, 4, or 7 days in a humid incubator at 37° C. and at 5%CO₂. Calcein AM and Ethidium homodimer-1 were used to stain live/deadcells. The cell images were captured under a fluorescent microscope.

Glass-ceramic discs were prepared from cerammed parts. The precursorglass patties were cerammed in an electronic furnace using a cycle of700° C. for 2 hr for nucleation and then 800° C. for 4 hr for crystalgrowth. After ceramming, parts (50.8 mm×50.8 mm×1.0 mm thick) were cutfrom the patties using a diamond saw, and then ground and polished to a1.0 micron finish using CeO₂ slurry. All finished parts were cleaned bysonicating in an ultrasonic sonicater for 10 min.

Ion exchange was accomplished by immersing the finished parts in aNaNO₃, in a KNO₃, or a bath containing a mixture both salts. The bathwas first heated up to 470° C. to obtain a molten salt and then partswere immersed for a suitable time for adequate ion exchange. Theion-exchanged parts were rinsed thoroughly with water and air dry priorto mechanical testing. Flexural strength was tested according to ASTMC1499-15. A ring on ring test-jig equipped with an Instron testingmachine with a ring support of 25.4 mm in diameter and a loading ring of12.7 mm in diameter was performed on finished samples. Flexural strengthwas determined based on the abovementioned ASTM procedure.

FIG. 2 was a listing of flexural strength from different compositions(200 to 260) from literature and compared to the flexural strength ofthe disclosed ion exchanged composition (270). The test procedure forexample compositions was detailed in the example for FIG. 1.

The disclosure has been described with reference to various specificembodiments and techniques. However, many variations and modificationsare possible while remaining within the scope of the disclosure.

What is claimed is:
 1. A method of making a bioactive glass-ceramicarticle comprising: forming a melt mixture of a source of: 50 to 75 wt %SiO₂, 1 to 5 wt % Al₂O₃, 0.1 to 10% B₂O₃, 5 to 20 wt % Li₂O, 0.5 to 5 wt% Na₂O, 0.1 to 4% K₂O, 0.5 to 6 wt % P₂O₅ 0.5 to 8% ZrO₂, and 0.1 to 1.0wt % F⁻, based on a 100 wt % total of the composition to form aglass-ceramic article; forming an article from the melt; andaccomplishing at least one chemical strengthening of the resultingglass-ceramic article.
 2. The method of making a bioactive glass-ceramicarticle of claim 1 wherein the article comprises a pattie, a dimensionedportion cut from a pattie, a plurality of particles, a drawn sheet, adrawn fiber, or combinations thereof.
 3. The method of making abioactive glass-ceramic article of claim 1 further comprising annealingthe article prior to accomplishing at least one chemical strengthening.4. The method of claim 1 wherein the at least one chemical strengtheningof the resulting glass-ceramic article is accomplished for a suitabletime by ion exchanging in a NaNO₃ bath to exchange out lithium ions,exchanging in a KNO₃ bath to exchange out lithium ions and sodium ionsfrom the surface of the article, or exchanging in a NaNO₃ and KNO₃ bathto exchange out lithium ions from the surface of the article.
 5. Themethod of claim 1 wherein the bioactive glass-ceramic article has abioactivity after ion-exchanging.